• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Infection and immunity >Differential Effects of Total and Partial Neutralization of Tumor Necrosis Factor on Cell-Mediated Immunity to Mycobacterium bovis BCG Infection
【24h】

Differential Effects of Total and Partial Neutralization of Tumor Necrosis Factor on Cell-Mediated Immunity to Mycobacterium bovis BCG Infection

机译：肿瘤坏死因子对细胞介导的免疫细胞植物杆菌BCG感染的差异和部分中和

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The effects of total and partial inhibition of tumor necrosis factor (TNF) on sensitivity to Mycobacterium bovis BCG infection were investigated by using transgenic mice in which hepatocytes produced different amounts of human soluble TNF receptor 1 (sTNFR1) fused to the Fc fragment of human immunoglobulin G3 that could be detected in the serum. Transgenic mice expressing high serum levels of sTNFR1, neutralizing all circulating TNF, failed to develop differentiated granulomas and bactericidal mechanisms, and they succumbed to BCG infection. sTNFR1 transgenic mice did not activate BCG-induced Th1-type cytokines early in infection, but uncontrolled cytokine release was found late in infection. In this work we also evaluated the effect of partial inhibition of TNF on resistance to BCG infection. Transgenic mice expressing low levels of sTNFR1 were protected against BCG infection, and they developed increased bactericidal mechanisms, such as enhanced inducible nitric oxide synthase activity, increased macrophage activation, and showed higher numbers of liver granulomas early in infection compared to their negative littermates. Our data suggest that while total inhibition of TNF prevented BCG-induced cell-mediated immune responses, partial inhibition of TNF could contribute to macrophage activation, induction of bactericidal mechanisms, and granuloma formation in the early phase of BCG infection.
机译：通过使用转基因小鼠研究了肝细胞的转基因小鼠，研究了肿瘤坏死因子（TNF）对敏感性BOVIS BCG感染的影响。肝细胞产生不同量的人可溶性TNF受体1（STNFR1）融合对于可以在血清中检测的人免疫球蛋白G3的Fc片段。表达高血清STNFr1的转基因小鼠，中和所有循环TNF，未能显影分化的肉芽肿和杀菌机制，并且它们持续到BCG感染。 STNFR1转基因小鼠早期未激活BCG诱导的TH1型细胞因子，但感染后积会发现不受控制的细胞因子释放。在这项工作中，我们还评估了部分抑制TNF对BCG感染抗性的影响。表达低水平的STNFR1的转基因小鼠免受BCG感染，并且它们产生了增加的杀菌机制，例如增强的诱导型一氧化氮合酶活性，增加的巨噬细胞活化，并与其负凋落物相比，感染的早期肝肉芽肿会较高。我们的数据表明，虽然TNF的总抑制阻止BCG诱导的细胞介导的免疫反应，但部分抑制TNF可以有助于巨噬细胞激活，诱导杀菌机制，并在BCG感染早期术后肉芽肿形成。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号